Doxorubicin Chemomyectomy

Chronic spasms in facial and cervical skeletal muscle can often be painful
and functionally disabling. Common treatments for these disorders
include oral medications, surgical denervation of the affected muscle
groups and, more commonly, injection of botulinum toxin into the
affected muscle. The effects of botulinum toxin are temporary and
require reinjection every 3-4 months for treatment of cervical dystonia.
Furthermore, botulinum in higher doses can cause systemic problems
distant from the injection site. Meanwhile, patients can also produce
antibodies to the toxin, rendering it ineffective for future treatment.

In comparison, doxorubicin is a myotoxin that causes loss of myofibers,
resulting in a permanent reduction of uncontrolled muscle spasms.
Studies in our lab have focused on identifying the effectiveness
of using doxorubicin for the treatment of cervical dystonia. These
studies involved directly injecting doxorubicin into rabbit sternocleidomastoid,
a large neck muscle, and identifying changes in that muscle group
over 1 to 6 months. In vitro [1] and in situ [2] studies showed
that doxorubicin-treated sternocleidomastoid muscle produced less
force than untreated muscles; further, histological studies showed
that doxorubicin reduced muscle cross-sectional area between 75-98%
over control [3]. Additionally, the remaining fibers contained a
higher proportion of slow and neonatal myosin heavy chain isoforms.

From a translational research perspective, our lab has also developed
a force assessment approach for measuring human sternocleidomastoid
function in vivo [4]. Thus, we have means to assess the relative
effectiveness of a given experimental approach in a human patient
population.